We previously described the development of glomerulosclerosis in mice transgenic for large T-antigen, a gene whose in vitro expression markedly increases proliferation of cultured cells. In the current study we sought to determine the effect of unilateral nephrectomy on these sclerosis-prone animals which have a genetically defined potential for increased renal growth. In comparison with sham nephrectomy animals, nephrectomized transgenic female mice had significantly larger kidneys, larger glomeruli, more cells per glomerulus and more severe glomerulosclercisis. Nephrectomized transgenic male animals had variable increases in kidney size, no significant increase in glomerular size or cellularity, and no worsening of glomerulosclerosis. In non-transgenic female animals nephrectomy induced an increase in kidney size but not in glomerular size and failed to induce glomerular lesions. A close correlation was found between glomerular size and severity of glomerulosclerosis in these animals.